Translational Bioinformatics for Diagnostic and Prognostic Prediction of Prostate Cancer in the Next-Generation Sequencing Era

The discovery of prostate cancer biomarkers has been boosted by the advent of next-generation sequencing (NGS) technologies. Nevertheless, many challenges still exist in exploiting the flood of sequence data and translating them into routine diagnostics and prognosis of prostate cancer. Here we review the recent developments in prostate cancer biomarkers by high throughput sequencing technologies. We highlight some fundamental issues of translational bioinformatics and the potential use of cloud computing in NGS data processing for the improvement of prostate cancer treatment.

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Profiling DNA Methylation Based on Next-Generation Sequencing Approaches: New Insights and Clinical Applications

Genes ◽

10.3390/genes9090429 ◽

2018 ◽

Vol 9 (9) ◽

pp. 429 ◽

Cited By ~ 38

Author(s):

Daniela Barros-Silva ◽

C. Marques ◽

Rui Henrique ◽

Carmen Jerónimo

Keyword(s):

Dna Methylation ◽

Next Generation Sequencing ◽

High Throughput Sequencing ◽

Epigenetic Modification ◽

Response To Therapy ◽

Next Generation ◽

Sequencing Technologies ◽

Prognosis And Prediction ◽

Novel Biomarkers ◽

Generation Sequencing

DNA methylation is an epigenetic modification that plays a pivotal role in regulating gene expression and, consequently, influences a wide variety of biological processes and diseases. The advances in next-generation sequencing technologies allow for genome-wide profiling of methyl marks both at a single-nucleotide and at a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, coverage, and bioinformatics analysis. Thus, the selection of the most feasible method according with the project’s purpose requires in-depth knowledge of those techniques. Currently, high-throughput sequencing techniques are intensively used in epigenomics profiling, which ultimately aims to find novel biomarkers for detection, diagnosis prognosis, and prediction of response to therapy, as well as to discover new targets for personalized treatments. Here, we present, in brief, a portrayal of next-generation sequencing methodologies’ evolution for profiling DNA methylation, highlighting its potential for translational medicine and presenting significant findings in several diseases.

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Non-coding RNA bioinformatics platform for full backing of the high-throughput sequencing experiments generated by next-generation sequencing technologies

EMBnet journal ◽

10.14806/ej.18.a.461 ◽

2012 ◽

Vol 18 (A) ◽

pp. 132

Author(s):

F Licciulli ◽

A Consiglio ◽

G De Caro ◽

A Gisel ◽

G Grillo ◽

...

Keyword(s):

Next Generation Sequencing ◽

High Throughput ◽

High Throughput Sequencing ◽

Next Generation ◽

Sequencing Technologies ◽

Non Coding Rna ◽

Generation Sequencing

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Next-Generation Sequencing in Newborn Screening: A Review of Current State

Frontiers in Genetics ◽

10.3389/fgene.2021.662254 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ziga I. Remec ◽

Katarina Trebusak Podkrajsek ◽

Barbka Repic Lampret ◽

Jernej Kovac ◽

Urh Groselj ◽

...

Keyword(s):

Next Generation Sequencing ◽

Newborn Screening ◽

High Throughput Sequencing ◽

Successful Implementation ◽

Next Generation ◽

Screening Programs ◽

Sequencing Technologies ◽

Current State ◽

Time Required ◽

Generation Sequencing

Newborn screening was first introduced at the beginning of the 1960s with the successful implementation of the first phenylketonuria screening programs. Early expansion of the included disorders was slow because each additional disorder screened required a separate test. Subsequently, the technological advancements of biochemical methodology enabled the scaling-up of newborn screening, most notably with the implementation of tandem mass spectrometry. In recent years, we have witnessed a remarkable progression of high-throughput sequencing technologies, which has resulted in a continuous decrease of both cost and time required for genetic analysis. This has enabled more widespread use of the massive multiparallel sequencing. Genomic sequencing is now frequently used in clinical applications, and its implementation in newborn screening has been intensively advocated. The expansion of newborn screening has raised many clinical, ethical, legal, psychological, sociological, and technological concerns over time. This review provides an overview of the current state of next-generation sequencing regarding newborn screening including current recommendations and potential challenges for the use of such technologies in newborn screening.

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Assessment of Bioleaching Microbial Community Structure and Function Based on Next-Generation Sequencing Technologies

Minerals ◽

10.3390/min8120596 ◽

2018 ◽

Vol 8 (12) ◽

pp. 596 ◽

Cited By ~ 1

Author(s):

Shuang Zhou ◽

Min Gan ◽

Jianyu Zhu ◽

Xinxing Liu ◽

Guanzhou Qiu

Keyword(s):

Community Structure ◽

Next Generation Sequencing ◽

Microbial Ecology ◽

High Throughput ◽

High Throughput Sequencing ◽

Structure And Function ◽

Next Generation ◽

Sequencing Technologies ◽

And Function ◽

Generation Sequencing

It is widely known that bioleaching microorganisms have to cope with the complex extreme environment in which microbial ecology relating to community structure and function varies across environmental types. However, analyses of microbial ecology of bioleaching bacteria is still a challenge. To address this challenge, numerous technologies have been developed. In recent years, high-throughput sequencing technologies enabling comprehensive sequencing analysis of cellular RNA and DNA within the reach of most laboratories have been added to the toolbox of microbial ecology. The next-generation sequencing technology allowing processing DNA sequences can produce available draft genomic sequences of more bioleaching bacteria, which provides the opportunity to predict models of genetic and metabolic potential of bioleaching bacteria and ultimately deepens our understanding of bioleaching microorganism. High-throughput sequencing that focuses on targeted phylogenetic marker 16S rRNA has been effectively applied to characterize the community diversity in an ore leaching environment. RNA-seq, another application of high-throughput sequencing to profile RNA, can be for both mapping and quantifying transcriptome and has demonstrated a high efficiency in quantifying the changing expression level of each transcript under different conditions. It has been demonstrated as a powerful tool for dissecting the relationship between genotype and phenotype, leading to interpreting functional elements of the genome and revealing molecular mechanisms of adaption. This review aims to describe the high-throughput sequencing approach for bioleaching environmental microorganisms, particularly focusing on its application associated with challenges.

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Next-generation sequencing of primary prostate cancer tumors to reveal actionable opportunities for clinical management.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16582 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16582-e16582

Author(s):

Daniel James Crona ◽

Anthony Drier ◽

Jing Daisy Zhu ◽

Emily Fox Bell ◽

Margaret Rose Sketch ◽

...

Keyword(s):

Prostate Cancer ◽

Next Generation Sequencing ◽

Sequence Data ◽

Copy Number Variations ◽

Parp Inhibition ◽

Precision Oncology ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Primary Prostate Cancer ◽

Generation Sequencing

e16582 Background: The Strata Trial (NCT03061305) is a multi-institutional precision oncology collaboration structured as an observational protocol that aims to match patients to genomically guided therapies. Methods: Selected University of North Carolina (UNC) metastatic prostate cancer (mPC) patients were enrolled on this IRB-approved study. Formalin fixed paraffin-embedded primary tumor specimens, without matched germline controls, were sent for targeted next generation sequencing (NGS) to detect actionable variants, including: mutations in 87 genes, copy number variations in 31 genes, gene fusions in 46 gene drivers, and microsatellite instability (MSI) status. mPC-related genes of specific interest included: AR, ATM, BRCA1/2, ERG, MSH2, MSH6, PTEN, RB1, and TP53. Results: Of the 108 cases sequenced, 6 (6%) failed testing. Of the 102 mPC patients with sequence data, the median age was 69 (47-86), 60 (59%) were white, 35 (34%) were black, 1 (1%) was Asian, and 6 (6%) declined to identify race. NGS data revealed 122 variants in 27 genes: 73 patients (71%) had at least one variant. Among those 73 patients, 38 (52%) had only 1 variant, 24 (33%) had 2 variants, 8 (11%) had 3 variants, and 3 (4%) had 4 variants. TMPRSS2-ERG fusions occurred most frequently (51%), followed by TP53 variants (38%), and PTEN variants (16%). Only 8% of patients had variants in DNA damage repair genes, including ATM (3%), BRCA2 (3%) and MSH2 (2%). Two patients with MSI high tumors were treated with pembrolizumab, while 4 patients with deep BRCA2 or ATM deletions were eligible for trials of PARP inhibition. Conclusions: Our UNC experience shows that a high proportion of primary prostate cancer tumors from mPC patients have genomic variants, and two patients were treated based on these data. Limited actionability may reflect the landscape of currently FDA approved mPC treatments available clinical trials, or due to short duration of follow-up after enrollment on the Strata Trial.

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Prospective Cohort Study of Next-Generation Sequencing as a Diagnostic Modality for Unexplained Encephalitis in Children

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piz032 ◽

2019 ◽

Vol 9 (3) ◽

pp. 326-333 ◽

Cited By ~ 9

Author(s):

Julia C Haston ◽

Christina A Rostad ◽

Robert C Jerris ◽

Sarah S Milla ◽

Courtney McCracken ◽

...

Keyword(s):

Next Generation Sequencing ◽

Prospective Cohort ◽

High Throughput Sequencing ◽

Sequence Data ◽

Parvovirus B19 ◽

Cohort Analysis ◽

Human Bocavirus ◽

Next Generation ◽

Diagnostic Modality ◽

Generation Sequencing

Abstract Background Encephalitis is an inflammatory condition of the brain associated with long-term neurologic sequelae and even death in children. Although viruses are often implicated, an etiology is not identified in the majority of cases. Metagenomics-based next-generation sequencing (mNGS) is a high-throughput sequencing technique that can enhance the detection of novel or low-frequency pathogens. Methods Hospitalized immunocompetent children aged 6 months to 18 years with encephalitis of unidentified etiology were eligible for enrollment. Demographic, historical, and clinical information was obtained, and residual blood and cerebrospinal fluid (CSF) samples were subjected to mNGS. Pathogens were identified by querying the sequence data against the NCBI GenBank database. Results Twenty children were enrolled prospectively between 2013 and 2017. mNGS of CSF identified 7 nonhuman nucleic acid sequences of significant frequency in 6 patients, including that of Mycoplasma bovis, parvovirus B19, Neisseria meningitidis, and Balamuthia mandrillaris. mNGS also detected Cladophialophora species, tobacco mosaic virus, and human bocavirus, which were presumed to be contaminants or nonpathogenic organisms. One patient was found to have positive serology results for California encephalitis virus, but mNGS did not detect it. Patients for whom mNGS identified a diagnosis had a significantly higher CSF white blood cell count, a higher CSF protein concentration, and a lower CSF glucose level than patients for whom mNGS did not identify a diagnosis. Conclusion We describe here the results of a prospective cohort analysis to evaluate mNGS as a diagnostic tool for children with unexplained encephalitis. Although mNGS detected multiple nonpathogenic organisms, it also identified multiple pathogens successfully and was most useful in patients with a CSF abnormality.

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Bioinformatics Strategies, Challenges, and Opportunities for Next Generation Sequencing-Based HLA Genotyping

Transfusion Medicine and Hemotherapy ◽

10.1159/000502487 ◽

2019 ◽

Vol 46 (5) ◽

pp. 312-325 ◽

Cited By ~ 6

Author(s):

Steffen Klasberg ◽

Vineeth Surendranath ◽

Vinzenz Lange ◽

Gerhard Schöfl

Keyword(s):

Next Generation Sequencing ◽

Sequence Data ◽

Rapid Evolution ◽

Human Leukocyte ◽

Next Generation ◽

Sequencing Data ◽

Sequencing Technologies ◽

Hla Genotyping ◽

Sequencing Platforms ◽

Generation Sequencing

The advent of next generation sequencing (NGS) has altered the face of genotyping the human leukocyte antigen (HLA) system in clinical, stem cell donor registry, and research contexts. NGS has led to a dramatically increased sequencing throughput at high accuracy, while being more time and cost efficient than precursor technologies. This has led to a broader and deeper profiling of the key genes in the human immunogenetic make-up. The rapid evolution of sequencing technologies is evidenced by the development of varied short-read sequencing platforms with differing read lengths and sequencing capacities to long-read sequencing platforms capable of profiling full genes without fragmentation. Concomitantly, there has been development of a diverse set of computational analyses and software tools developed to deal with the various strengths and limitations of the sequencing data generated by the different sequencing platforms. This review surveys the different modalities involved in generating NGS HLA profiling sequence data. It systematically describes various computational approaches that have been developed to achieve HLA genotyping to different degrees of resolution. At each stage, this review enumerates the drawbacks and advantages of each of the platforms and analysis approaches, thus providing a comprehensive picture of the current state of HLA genotyping technologies.

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